Interactions of Genes and Childhood Adversity in the Lifetime Dynamics of Cognitive Abilities Behavior genetic research implicates the substantial role of genetic variation in contributing to individual differences in cognitive abilities, with genetic variance reported as high as 80-90%. Despite this, attempts to identify specific genes that contribute to normal-range variation in cognition have thus far been disappointing. The lack of replicated results may be due in part to three methodological weaknesses. First, many studies have used a single global measure of cognition (typically labeled "IQ") that is etiologically and conceptually complex. Results from studies of twins indicate that genetic factors contribute differently to different domains of cognition, including memory, speed of processing, and fluid reasoning. Use of measures that assess more basic cognitive processes should help in efforts to identify genes influencing cognitive abilities. Second, most measured gene studies of cognition have used measures of cognition obtained at a single occasion. For providing information about cognitive decline associated with aging, it is more relevant to study the genetic influences on cognitive trajectories, rather than absolute level of performance at a single time point. Third, prior studies have focused on identifying average effects of specific genes and rarely include measured environmental factors. Evidence from human and animal studies indicates the importance of specific environmental impacts on later cognition, including health insults and socio-cultural factors. In sum, a clearer understanding of the basis for variation in cognition and cognitive decline could be obtained by using measured genes and environmental risk factors obtained from samples assessed using multiple measures of cognition and studied prospectively from early childhood through senescence. The proposed project will address these issues using a sample of more than 400 individuals measured repeatedly on multiple tests from infancy through older age (70s-80s). This application is for a competitive supplement to AG-07407-14, "Assessing and Improving Cognitive Measures in the HRS." One aspect of this project is to study the dynamics of change in cognitive abilities among participants in the Intergenerational Studies, a collection of 3 longitudinal studies of individuals from infancy to old age who have been repeatedly assessed on cognitive, psychological, health and socioeconomic information. The goals of the current application are to: (1) genotype 1200 participants from these samples using 50 candidate genes on pathways for processes involved in learning, memory, and cognitive functioning;(2) study the relation of variation in these genes to life-span trajectories of cognitive abilities;(3) study how genetic variation interacts with early childhood adversity and other environmental risk factors to influence trajectories of cognitive change. PUBLIC HEALTH RELEVANCE: This project will further the understanding of how genes and environmental risk factors work together to affect cognitive abilities such as memory, reasoning, and problem solving, and how these abilities change across the lifespan. Results will help guide interventions to reduce cognitive decline associated with aging.